on Journal of neurology
by Prosperini L, Annovazzi P, Boffa L, Buscarinu MC, Gallo A, Matta M, Moiola L, Musu L, Perini P, Avolio C, Barcella V, Bianco A, Farina D, Ferraro E, Pontecorvo S, Granella F, Grimaldi LME, Laroni A, Lus G, Patti F, Pucci E, Pasca M, Sarchielli P,
In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.
on European journal of neurology
by Signoriello E, Lus G, Polito R, Casertano S, Scudiero O, Coletta M, Monaco ML, Rossi F, Nigro E, Daniele A
Adiponectin is a cytokine linking energy metabolism and immune system. After being assembled, adiponectin circulates as oligomers of different molecular weight, i.e. low, medium and high (HMW) molecular weight. These have the most potent biological effects. Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system. The aim of this study was to characterize the expression levels of both total adiponectin and its oligomerization state in the serum from 99 patients with MS at baseline (i.e. not influenced by therapies). We also investigated the potential relationships between adiponectin and disease progression and severity.
on Frontiers in behavioral neuroscience
by Barbarulo AM, Lus G, Signoriello E, Trojano L, Grossi D, Esposito M, Costabile T, Lanzillo R, Saccà F, Morra VB, Conchiglia G
Few studies examined the effects of combined motor and cognitive rehabilitation in patients with multiple sclerosis (MS). The present prospective, multicenter, observational study aimed to determine the efficacy of an integrated cognitive and neuromotor rehabilitation program versus a traditional neuromotor training on walking, balance, cognition and emotional functioning in MS patients. Sixty three MS patients were selected and assigned either to the Integrated Treatment Group (ITG; = 32), receiving neuropsychological treatment (performed by ERICA software and paper-pencil tasks) complemented by conventional neuromotor rehabilitation, or to the Motor Treatment Group ( = 31) receiving neuromotor rehabilitation only. The intervention included two 60-min sessions per week for 24 weeks. At baseline and at end of the training all patients underwent a wide-range neuropsychological, psychological/emotional, and motor assessment. At baseline the two groups did not differ for demographic, neuropsychological, psychological/emotional, and motor features significantly. After rehabilitation, only ITG group significantly ( for False Discovery Rate) improved on test tapping spatial memory, attention and cognitive flexibility, as well as on scales assessing depression and motor performance (balance and gait). A regression analysis showed that neuropsychological and motor improvement was not related to improvements in fatigue and depression. The present study demonstrated positive effects in emotional, motor, and cognitive aspects in MS patients who received an integrated cognitive and neuromotor training. Overall, results are supportive of interventions combining motor and cognitive training for MS.
on Journal of the neurological sciences
by Signoriello E, Cirillo M, Puoti G, Signoriello G, Negro A, Koci E, Melone MAB, Rapacciuolo A, Maresca G, Lus G
To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura.
on Neurodegenerative disease management
by Lus G, Cantello R, Danni MC, Rini A, Sarchielli P, Tassinari T, Signoriello E
Complaints about Δ-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex; GW Pharma Ltd, Salisbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies. This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects.
on Multiple sclerosis and related disorders
by Signoriello E, Landi D, Monteleone F, Saccà F, Nicoletti CG, Buttari F, Sica F, Marfia GA, Di Iorio G, Lus G, Centonze D
Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a.
on Quantitative imaging in medicine and surgery
by Schettino C, Caranci F, Lus G, Signoriello E, Eoli M, Anghileri E, Pollo B, Melone MAB, Di Iorio G, Finocchiaro G, Ugga L, Tedeschi E
We report the case of a young man with sudden onset of diplopia after an upper respiratory tract infection. Based on the first radiological findings acute hemorrhagic leukoencephalitis, a variant of acute disseminated encephalomyelitis, was suspected and treatment with high dose intravenous dexamethasone was started but it was stopped for intolerance. The patient clinically worsened, developing gait instability, ataxia and ophthalmoplegia; brain MRI performed 20 days later showed severe progression of the disease with subependymal dissemination. After brain biopsy of the right temporal lesion the histological diagnosis was glioblastoma. These findings suggest that MRI features of acute hemorrhagic leukoencephalitis may dissimulate the diagnosis of diffuse glioma/glioblastoma. This case underscores the importance of considering diffuse glioma in the differential diagnosis of atypical signs and symptoms of acute hemorrhagic leukoencephalitis and underlines the relevant role of integrating neuroradiologic findings with neuropathology.
on Annals of neurology
by Iaffaldano P, Simone M, Lucisano G, Ghezzi A, Coniglio G, Brescia Morra V, Salemi G, Patti F, Lugaresi A, Izquierdo G, Bergamaschi R, Cabrera-Gomez JA, Pozzilli C, Millefiorini E, Alroughani R, Boz C, Pucci E, Zimatore GB, Sola P, Lus G, Maimone D, Avolio C, Cocco E, Sajedi SA, Costantino G, Duquette P, Shaygannejad V, Petersen T, Fernández Bolaños R, Paolicelli D, Tortorella C, Spelman T, Margari L, Amato MP, Comi G, Butzkueven H, Trojano M, ,
To assess prognostic factors for a second clinical attack and a first disability worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of Multiple Sclerosis (MS) patients.
on Neurobiology of aging
by Coppola C, Saracino D, Puoti G, Lus G, Dato C, Le Ber I, Pariente J, Caroppo P, Piccoli E, Tagliavini F, Di Iorio G, Rossi G
Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases displaying high clinical, pathologic, and genetic heterogeneity. Several autosomal dominant progranulin (GRN) mutations have been reported, accounting for 5%-10% of FTLD cases worldwide. In this study, we described the clinical characteristics of 7 Italian patients, 5 with a diagnosis of frontotemporal dementia behavioral variant and 2 of corticobasal syndrome (CBS), carrying the GRN deletion g.101349_101355delCTGCTGT, resulting in the C157KfsX97 null mutation, and hypothesized the existence of a founder effect by means of haplotype sharing analysis. We performed plasma progranulin dosage, GRN gene sequencing, and haplotype sharing study, analyzing 10 short tandem repeat markers, spanning a region of 11.08 Mb flanking GRN on chromosome 17q21. We observed shared alleles among 6 patients for 8 consecutive short tandem repeat markers spanning a 7.29 Mb region. Therefore, also with this particular mutation, the elevated clinical variability described among GRN-mutated FTLD cases is confirmed. Moreover, this is the first study reporting the likely existence of a founder effect for C157KfsX97 mutation in Southern Italy.
on Multiple sclerosis (Houndmills, Basingstoke, England)
by Saccà F, Costabile T, Carotenuto A, Lanzillo R, Moccia M, Pane C, Russo CV, Barbarulo AM, Casertano S, Rossi F, Signoriello E, Lus G, Brescia Morra V
Despite cognitive tests have been validated in multiple sclerosis (MS), a neuropsychological evaluation is not implemented in the Expanded Disability Status Scale (EDSS) scoring.